Several clinical studies have found that regular cannabis users tend to have higher bilirubin levels than non-users, and the likely explanation centers on how THC is processed in the liver. Bilirubin is a yellow pigment the body produces when it breaks down old red blood cells, and your liver clears it through a specific enzyme that THC also relies on for its own metabolism. That overlap creates a plausible mechanism for competition, and the clinical data, while still limited in size and scope, consistently point in the same direction.
What the Studies Actually Show
Multiple studies comparing cannabis users to non-users have measured bilirubin as part of broader liver function panels, and the results are remarkably consistent. One study found that the mean bilirubin level in marijuana smokers was about 39% higher than in healthy controls, a difference that was statistically significant. Smokers averaged around 1.1 mg/dL compared to 0.67 mg/dL in the control group.1Nature and Science. Impact of marijuana smoking on liver and sex hormones: Correlation with oxidative stress Another study reported that cannabis users showed higher total bilirubin, direct bilirubin, and indirect bilirubin compared to controls.2Global Journal of Addiction & Rehabilitation Medicine. Effect of Cannabis Abuse and Ezymatic Alterations to Endorse Liver Dysfunctions A third investigation from a psychiatric hospital in Ghana confirmed that both direct and indirect bilirubin were significantly elevated across substance-user groups, including cannabis users.3PubMed Central. Cannabis and Alcohol Use and Their Effects on Hematological and Biochemical Parameters: Evidence From the Accra Psychiatric Hospital, Ghana
To be clear, the elevations seen in these studies were generally modest. Most cannabis users still had bilirubin values within or just above the normal clinical range. This is not the kind of dramatic spike you would see with, say, hepatitis or a blocked bile duct. But the pattern is consistent enough across different populations and study designs that it is unlikely to be random noise.
Do Bilirubin Levels Come Back Down After Stopping?
One of the more useful pieces of evidence comes from a study that tracked cannabis users before and after addiction treatment. At admission, the cannabis-user group had significantly elevated total bilirubin compared to controls. After treatment, when the participants had stopped using cannabis, their bilirubin values dropped significantly compared to their admission levels.4PLOS ONE. Health status outcome among cannabis addicts after treatment of addiction The same pattern held for other liver markers like ALT and AST. This reversal is important because it suggests the bilirubin elevation is a functional effect of ongoing cannabis use rather than a sign of permanent liver damage. Once the liver is no longer dealing with THC, it catches up on clearing bilirubin.
Why THC and Bilirubin Compete for the Same Pathway
Your liver clears bilirubin through a process that involves several steps. First, bilirubin gets pulled into liver cells with the help of transporter proteins. Once inside, an enzyme called UGT1A1 attaches a sugar molecule to bilirubin, making it water-soluble so it can be excreted into bile and eventually leave your body through stool.5PubMed. Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia That enzyme, UGT1A1, is the critical bottleneck. It is the same enzyme that is underactive in people with Gilbert’s syndrome, a common and harmless genetic condition that causes mildly elevated bilirubin.
Here is where THC enters the picture. THC is also metabolized partly through UGT enzymes, including UGT1A1 and UGT1A9. A review examining the overlap between THC and the chemotherapy drug irinotecan identified shared metabolism through UGT1A1 as one of the key pathways where these compounds could interfere with each other.6Springer Link / Clin Drug Investig. High Doses of Δ(9)-Tetrahydrocannabinol Might Impair Irinotecan Chemotherapy: A Review of Potentially Harmful Interactions If THC is occupying UGT1A1’s attention, bilirubin processing slows down, and blood levels rise. This is the same basic mechanism by which several prescription drugs are known to cause mild hyperbilirubinemia.
Cannabinoids more broadly have been studied for their interactions with drug-metabolizing enzymes, including both the cytochrome P450 family (which handles the initial chemical breakdown of many drugs) and the UGT family (which handles a later step called conjugation). Much of what researchers know about these interactions comes from lab studies rather than large human trials, but the enzymatic competition is well-documented at the molecular level.7Taylor & Francis Online / Expert Review of Clinical Pharmacology. Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy
Does This Mean Cannabis Damages Your Liver?
Elevated bilirubin alone is not liver damage. Bilirubin is just one number on a liver function panel, and mild elevations from enzyme competition are a different animal from the kind of bilirubin spikes caused by actual liver injury. To understand whether cannabis harms the liver directly, you need to look at the bigger picture.
Cannabis interacts with the liver through two types of cannabinoid receptors, CB1 and CB2, which are expressed in liver cells. In chronic liver disease, the expression of both receptors tends to increase. Stimulating CB1 receptors promotes inflammation and fibrosis (scarring), while activating CB2 receptors appears to have the opposite effect, inhibiting fibrosis.8PubMed Central. Cannabinoids and the endocannabinoid system in liver diseases This dual nature makes the relationship between cannabis and liver health genuinely complicated. In people with existing chronic liver disease like hepatitis B, higher expression of CB1 receptors has been linked to more advanced fibrosis, and the activated liver cells responsible for scarring were found to express CB1.9PubMed. Hepatic expression of cannabinoid receptors CB1 and CB2 correlate with fibrogenesis in patients with chronic hepatitis B
For someone with a healthy liver who uses cannabis occasionally, the bilirubin elevation is almost certainly benign, more akin to the fluctuations seen with Gilbert’s syndrome than a sign of progressing liver disease. But for people with pre-existing liver conditions, the picture is murkier. The endocannabinoid system is deeply embedded in liver biology, and regular cannabis exposure adds a variable that researchers are still sorting out.10PubMed Central. Endocannabinoids in liver disease
When Elevated Bilirubin Actually Matters
If you use cannabis and your blood work comes back with mildly elevated bilirubin, the first question your doctor will ask is whether there are other abnormal liver markers. Bilirubin by itself, sitting a little above the reference range, usually prompts a repeat test or a shrug. When bilirubin rises alongside liver enzymes like ALT and AST, or when it keeps climbing over time, that is a different situation that warrants further investigation.
For cannabis users specifically, this creates a practical issue. If you do not tell your doctor about your cannabis use, they may order follow-up imaging or blood work chasing a cause for elevated bilirubin that has a straightforward explanation. Being upfront about cannabis use helps your doctor avoid unnecessary testing and focus on anything that genuinely needs attention. It is worth remembering that about 5-10% of the general population has Gilbert’s syndrome, which causes the same kind of mild bilirubin bump. If you already have Gilbert’s syndrome and also use cannabis regularly, the two effects could stack, potentially pushing your bilirubin above the range where it would normally be written off as harmless.11PubMed. Expression and inducibility of the human bilirubin UDP-glucuronosyltransferase UGT1A1 in liver and cultured primary hepatocytes: evidence for both genetic and environmental influences
CBD, THC, and How Product Type Matters
Most of the clinical studies cited above involved cannabis use generally, which means the participants were primarily using THC-containing products. But the cannabinoid market has expanded enormously, and many people now take CBD products either alone or in combination with THC. CBD raises its own liver-related concerns. A systematic review and meta-analysis on CBD-associated liver toxicity concluded that clinicians should screen for CBD use and monitor liver function in patients who may be at increased risk.12PubMed. Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis
This is relevant because CBD, like THC, is metabolized through the liver and competes for some of the same enzymatic pathways. Whether CBD affects bilirubin through the same UGT1A1 competition as THC is less clearly established in human studies, but the theoretical basis is there. And high-dose CBD, the kind used in FDA-approved epilepsy medication, has caused clinically significant liver enzyme elevations in some patients, particularly those also taking other hepatically metabolized drugs like clobazam.
A case report illustrates the extreme end of this spectrum. A two-year-old child with seizures being treated with multiple anticonvulsants was also given nonprescription hemp extract (a CBD-containing product) by his parents. He developed severe liver dysfunction, with elevated coagulation markers indicating the liver was struggling. His liver enzymes gradually improved after the hemp product was stopped.13J Am Pharm Assoc. Severe liver dysfunction in a toddler receiving nonprescription phytocannabinoid While this case involved a very young child on multiple medications, and the phytocannabinoid product may have been poorly regulated, it underscores that cannabinoid products can cause real hepatic stress when combined with other drugs that tax the liver.
Drug Interactions That Amplify the Effect
The bilirubin question becomes more clinically meaningful when cannabis use overlaps with medications that also depend on UGT1A1 or other liver enzymes. The most studied example involves irinotecan, a chemotherapy drug. Both THC and irinotecan undergo first-pass metabolism in the liver through CYP3A4 and glucuronidation through UGT1A1. They also share transport pathways for getting their metabolites out of liver cells and into bile. A review examining this overlap raised concerns that heavy THC use could impair irinotecan metabolism at multiple points, potentially increasing the drug’s toxicity.6Springer Link / Clin Drug Investig. High Doses of Δ(9)-Tetrahydrocannabinol Might Impair Irinotecan Chemotherapy: A Review of Potentially Harmful Interactions
Irinotecan is a specific case, but the principle applies more broadly. Any drug that depends heavily on UGT1A1 for clearance could theoretically be affected by concurrent THC use, and that enzymatic competition could also further slow bilirubin processing. Other drugs known to interact with UGT1A1 include certain HIV antiretrovirals (like atazanavir, which famously causes jaundice through this exact mechanism) and some antibiotics. If you are taking any medication that your pharmacist has flagged as potentially causing jaundice or elevated bilirubin, adding regular THC use on top of it is worth discussing with your prescriber.
Severe Toxicity From Non-Standard Routes
While most cannabis users experience only mild, reversible bilirubin changes, there are documented cases of more serious hepatic events from unusual forms of cannabis use. An older case series described patients who developed jaundice after using intravenous cannabis tea, a preparation that is far outside normal recreational or medical use. Those patients experienced a range of severe symptoms including gastrointestinal bleeding, splenomegaly, and persistent low blood sugar alongside the jaundice.14PubMed Central. Adverse Effects of Intravenous Cannabis Tea These cases are not representative of what happens with standard smoked, vaped, or oral cannabis, but they illustrate that the route and preparation matter enormously. Injecting plant material directly into the bloodstream introduces contaminants that can cause acute liver and systemic damage far beyond anything attributable to THC itself.
What Standard Blood Work Cannot Tell You
A routine liver panel measures total bilirubin, and sometimes splits it into direct (conjugated) and indirect (unconjugated) fractions. The distinction is useful here. When bilirubin rises because UGT1A1 is being outcompeted, you would expect the indirect fraction to climb, since indirect bilirubin is the form that has not yet been processed by UGT1A1. In contrast, when bilirubin rises because of bile duct obstruction or liver cell death, the direct fraction tends to dominate.
The studies on cannabis users generally found elevations in both fractions, but the indirect component was consistently elevated.2Global Journal of Addiction & Rehabilitation Medicine. Effect of Cannabis Abuse and Ezymatic Alterations to Endorse Liver Dysfunctions This pattern is consistent with enzymatic competition rather than structural liver disease, and it aligns with the UGT1A1 competition theory. For a clinician reading your blood work, knowing that you use cannabis regularly would make this pattern immediately recognizable and far less alarming than it might otherwise appear.
One caveat: standard blood tests cannot distinguish between bilirubin elevation caused by cannabis and elevation caused by Gilbert’s syndrome, hemolysis (red blood cell breakdown), or other conditions. The mechanism produces a similar-looking result on paper. Context matters, and that context includes your medication list and your substance use.
Confounders Worth Acknowledging
Most studies comparing cannabis users to non-users face the same methodological challenge: people who use cannabis heavily often differ from non-users in other ways that affect liver function. They may drink more alcohol, use other substances, eat differently, or have different patterns of medication use. Some of the studies discussed here attempted to control for alcohol use and other variables, but none of them were large randomized trials, which is the gold standard for ruling out confounders.
That said, the consistency of the bilirubin finding across different populations, study designs, and countries lends it more weight than any single study would have on its own. And the enzymatic mechanism provides a clear biological explanation that does not depend on confounders at all: THC competes with bilirubin for UGT1A1, and that competition is demonstrable in lab settings regardless of what else is happening in a person’s life. The human studies and the biochemistry tell the same story, which is reassuring even if no single study is definitive.
One factor that remains poorly studied is dose. The available research mostly categorizes people as users or non-users, without much granularity about how much or how often they consume cannabis. It is reasonable to expect that heavier use would produce larger bilirubin elevations, since more THC passing through the liver means more competition for UGT1A1. But that dose-response relationship has not been cleanly demonstrated in humans yet, and it is one of the bigger gaps in the current evidence.